Hepatitis C virus (HCV) is diffused worldwide, and it is responsible for potentially severe chronic liver disease and primary liver cancer. Chronic infection remains for life if not spontaneously eliminated and viral persistence profoundly impairs the efficiency of host’s immunity. Attempts have been made to develop an effective vaccine, but efficacy trials have met with failure. The availability of highly efficacious direct acting antivirals (DAA) has shed hopes for progressive elimination of chronic HCV infection; however, this approach requires a global monumental effort. Moreover, DAA treatment does not completely restore the normal immunologic homeostasis. Here we discuss the main immunological features of immune responses to HCV and the epigenetic scars that chronic viral persistence leaves behind.